VEGF-Expressing Mesenchymal Stem Cell Therapy for Safe and Effective Treatment of Pain in Parkinson's Disease

Cell Transplant. 2023 Jan-Dec:32:9636897221149130. doi: 10.1177/09636897221149130.

Abstract

Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that mediates the differentiation and function of vascular endothelial cells. VEGF has been implicated in modulating various pains. However, the effects of VEGF in Parkinson's disease (PD)-related pain have not been studied. The goal of this study was to understand the effects of VEGF-expressing mesenchymal stem cells (MSCs) on PD-related pain and the involved mechanisms. We used two types of MSCs: hAMSC-Vector-GFP and hAMSC-VEGF189-GFP in PD mice. Then, the expression of VEGF and the viability have been compared between two types of MSCs. To demonstrate the therapeutic effect of hAMSC-VEGF189-GFP, we transplanted each cell line in a PD mouse model. Head mechanical withdrawal thresholds were examined. hAMSC-VEGF189-GFP was associated with significantly increased VEGF expression and slightly increased viability, compared with hAMSC-Vector-GFP. The transplanted hAMSC-VEGF189-GFP significantly improved mechanical allodynia and inhibited transient receptor potential vanilloid 1 (TRPV1) expression in site. And such pain relief effects could be partially blocked by TRPV1 agonist. However, we did not observe tumor generation or neuron degeneration in hAMSC-VEGF189-GFP-transplanted animals. Taken together, our data suggest that hAMSC-VEGF189-GFP is safely therapeutically appropriate for treating PD-related pain. VEGF inhibits TRPV1 expression, which may contribute to its analgesic properties.

Keywords: Parkinson’s disease; mesenchymal stem cells; pain; transient receptor potential vanilloid 1; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelial Cells / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Mice
  • Pain / metabolism
  • Parkinson Disease* / metabolism
  • Parkinson Disease* / therapy
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors